Tanycyte BMAL1 regulates high-fat diet weight gain and shapes arcuate neurogenesis in female mice.

The hypothalamic radial-glia-like tanycyte population plays important and intertwined roles in metabolism, reproduction, and seasonality. Although these processes are circadian-regulated, the role of the molecular clock in tanycytes themselves has not yet been examined. We report that clock genes cycle with much higher amplitude in ventral tanycytes compared to more dorsal ependymocytes and that adult, tanycyte-specific knockout of core clock gene Bmal1 reduces diet-associated weight gain and fat mass in female mice. Fate mapping studies show that female mice have higher baseline tanycyte-derived neurogenesis than males, with many of the resulting neurons localizing to the feeding-relevant arcuate nucleus. Female but not male mice show reduced tanycyte-derived arcuate neurogenesis after adult Bmal1 deletion, with an increased proportion of newborn neurons acquiring a feeding-suppressing POMC neuropeptidergic fate. Together, our data support a role for tanycyte BMAL1 as a sex-specific regulator of body composition and hypothalamic adult neurogenesis.